Microcapsules containing suspensions of biologically active compounds

ABSTRACT

Microcapsules containing a suspension of a solid, biologically active compound in an organic, water-immiscible liquid and processes for their preparation.

this application is a division of application Ser. No. 08/354,409, filedDec. 12, 1994.

FIELD OF THE INVENTION

This invention relates to microencapsules which contain a solidbiologically active compound suspended in a liquid, and processes fortheir preparation and for the use of such microcapsules.

BACKGROUND AND PRIOR ART

Microcapsule technology has been in existence for a number of years.Microcapsules have a variety of uses, especially for containing dyes,inks, chemical reagents, pharmaceuticals, flavoring materials, and moreespecially agrochemicals, that is fungicides, bactericides,insecticides, herbicides and the like.

The development and uses of microencapsulation are described by GordonMarrs and Herbert B. Scher in Chapter 4 of "Controlled Delivery of CropProtection Agents" (London, Taylor and Francis, 1990). As discussed byMarrs and Scher, there are three methods of forming microcapsules: i)physical methods, ii) phase separation methods and iii) interfacialpolymerization.

In the third of these methods, the walls of microcapsules are generallyformed of polymeric material produced by a polymerization reaction whichpreferably takes place at the interface between two phases, usually anaqueous phase and a water-immiscible organic phase. Thus, they may beproduced from a water-in-oil emulsion or more usually an oil-in-wateremulsion.

A basic patent dealing with microcapsule technology is U.S. Pat. No.4,285,720. In this patent the walls of the microcapsules are producedfrom polymers formed by reactions of isocyanate monomers.

A second means of forming microcapsules by interfacial polymerization isdescribed in U.S. Pat. No. 4,956,129. In this patent polymericmicrocapsule walls are produced from etherified urea-formaldehydeprepolymers which undergo self-condensation polymerization under acidconditions.

Various improvements on these techniques have been suggested. Forexample, U.S. Pat. No. 4,140,516, describes the use of phase transfercatalysts while U.S. Pat. No. 4,448,929, describes the use of animproved protective colloid. However, in all these patents, the processhave been applied only to liquids, i.e., to materials which are liquidat ambient temperature or to solutions. Unfortunately, many biologicallyactive compounds are solids with high melting points and are not readilysoluble in most commonly used solvents. The benefits ofmicroencapsulation e.g., controlled release and increased longevity ofefficacy have not been readily available to such compounds using knowntechniques.

It is also known to surround solids by a polymer matrix. Thus, in U.S.Pat. No. 4,428,983, there is described a process for producing quartzcrystals in a polymer matrix. The patent uses the term suspension fordescribing the paste of quartz crystals in the prepolymer, but thispublication does not describe the production of microcapsules containinga solid suspended in a liquid.

There are a large number of publications dealing with the production andapplication of microencapsulated formulations of haloacetanilideherbicides. These include U.S. Pat. Nos. 4,280,833; 4,417,916;4,534,783; 4,563,212; and 4,640,709. Additionally, U.S. Pat. No.4,936,901 discloses herbicidal compositions which are dry flowablewater-dispersible granular formulations comprising a mixture ofmicro-capsules of a water-insoluble pesticide (including ahaloacetanilide herbicide) encapsulated within a polymeric shell walland at least one other pesticide which is nonencapsulated. Suchcompositions were necessary since no satisfactory techniques to producea microcapsule containing a solid, biologically activate herbicidesuspended in a liquid have been known.

It is not surprising that capsules containing a biologically activesolid suspended in a liquid have not been made up until the present timesince the problems to be faced in producing such a capsule areformidable. For example, in forming such capsules from an oil-in-wateremulsion, the following difficulties must be addressed:

Firstly, a stable suspension of the solid in a water-immiscible liquidmust be produced. If dispersants or surfactants are used, they must notinterfere with further processes of dispersion used in makingmicrocapsules.

Secondly, the suspension must be dispersed in water to produce stable,well dispersed droplets. For biologically active substances, it ispreferable to have very small drop lets of liquid dispersed in water topresent a high surface area in the resulting microcapsules. To producevery small droplets requires high shear forces which would tend to breakdown the droplets and/or release the solid from suspension. Surfactantsare usually required to achieve good dispersion and stable droplets.

Thirdly, the presence of one or more surfactants can make the disperseddroplet system unstable and the phenomenon of phase inversion may occuri.e., the water forms small droplets within the liquid, a water-in-oilemulsion.

Fourthly, the solid suspended in the water-immiscible liquid is liableto migrate to the aqueous phase, particularly when emulsifyingsurfactants are used.

SUMMARY OF THE INVENTION

It has now been found that the above problems can be overcome and it ispossible to produce microcapsulated compositions containing a solidbiologically active compound suspended in a liquid.

DETAILED DESCRIPTION OF THE INVENTION

In accordance with the invention, a microencapsulated formulation of asolid biologically active compound suspended in a liquid is produced byphase separation or interfacial polymerization techniques. The preferredtechnique is interfacial polymerization, especially producing thecapsules from an oil-in-water emulsion by procedures such as thosedescribed in U.S. Pat. No. 4,285,720, and U.S. Pat. No. 4,956,129,modified as described herein.

The solid, biologically active compound is preferably an agrochemicaland especially a herbicide.

Preferred herbicides are s-triazines, e.g., atrazine, simazine,propazine, cyprozine;

Sulphonylureas e.g., chlorsulfuron, chlorimuronethyl,metsulfuron-methyl, thiameturon-methyl; and

Triketones e.g., sulcotrione.

An especially preferred herbicide is atrazine.

Another suitable compound is the fungicide (E)-methyl2-[2-(6-(2-cyanophenoxy)pyrimidin-4-yloxy)phenyl]-3-methoxypropenoate.

The liquid in which the solid is suspended may suitably be a secondherbicide, especially a thiocarbamate or a haloacetanilide andpreferably acetochlor.

The haloacetanilides, particularly the subclass generally known asα-chloroacetanilides, are a well-known class of herbicidal agents andhave been used and proposed for use in a number of crop and non-cropapplications. Some of the better known members of this class includeα-chloro-6'-ethyl-N-(2-methoxy-1-methylethyl)-acetanilide (metolachlor),N-butoxymethyl-α-chloro-2', 6'-diethylacetanilide (butachlor),α-chloro-2',6'-diethyl-N-methoxymethylacetanilide (alachlor),2-chloro-N-(ethoxymethyl)-6'-ethyl-o-acetotoluidide (acetochlor) andα-chloro-N-isopropylacetanilide (propachlor). Many other compounds ofthis type are disclosed in numerous patents.

The thiocarbamates are a well known class of herbicide which includes

Molinate--S-ethyl hexahydro-1H-azepine-1-carbothioate

Butylate--S-ethyl diisobutylthiocarbamate

EPTC--ethyl dipropylthiolcarbamate

Triallate--2,3,3-trichloroallyl-diisopropylthiolcarbamate

Diallate--cis-1-trans-2,3-dichloroallyl-diisopropylthiolcarbamate

Vernolate--S-propyl dipropylthiolcarbamate

When the liquid is a herbicide, the microcapsules of the inventionsuitably contain 0.1-55% by weight of biologically active compounds.

The liquid may alternatively be any organic solvent which is immisciblewith water, does not dissolve the biologically active solid toappreciable extent and is polar enough to dissolve the prepolymers usedto form the walls of the microcapsules.

Suitable examples of such solvents are aromatic compounds such asxylenes or naphthalenes, especially Solvesso 200; aliphatic compoundsuch as alkyl esters, especially alkyl acetates, e.g., Exxate 700-Exxate1000; alkyl phthalates, such as diethyl phthalate, dibutylphthalate;alcohols, such as isopropyl alcohol; ketones, such as acetophenone,cyclohexanone. The solvent may be a mixture of more than are compound.

A safener for either herbicide may be present and many such safeners orantidotes as well known in the art. Preferred types for use withhaloacetanilide herbicides include dichloroacetamides such as dichlormid(N,N-diallyl dichloroacetamide); 2,2,5-trimethyl-3-dichloroacetyloxazolidine (R-29148), N-dichloroacetyl-1-oxa-4-azaspiro[4,5]decane(AD-67); 4-dichloroacetyl-2,3-dihydro-3-methyl-1,4-benzoxazine(CGA-154281);1-(dichloroacetyl)hexahydro-3,3,8a-trimethylpyrrolo-[1,2-a]-pyrimidin-6(2H)-oneand N-(1,3-dioxolan-2-yl-methyl)-N-(2-propenyl)-2,2-dichloroacetamide(PPG-1292).

These and other dichloroacetamides are described, for instance, in U.S.Pat. Nos. 4,124,372; 4,256,481; 4,294,764; 4,448,960; 4,601,745;4,618,361; 4,708,735 and 4,900,350. Additional known types of safenersor antidotes include certain oxime derivatives (U.S. Pat. Nos. 4,070,389and 4,269,775, for instance), thiazole carboxylic acids and derivatives(U.S. Pat. No. 4,199,506 for instance), haloacyltetrahydroisoquinolines(U.S. Pat. No. 4,755,218, for example), aryl cyclopropane carbonitriles(U.S. Pat. No. 4,859,232, for example) and 1,8-naphthalic acid, itsanhydride and derivatives.

Safeners or antidotes, when included, will usually be contained in theorganic or water-immiscible phase.

The preferred materials for the microcapsule is a polyurea, formed asdescribed in U.S. Pat. No. 4,285,720, or a urea-formaldehyde polymer asdescribed in U.S. Pat. No. 4,956,129. The polyurea is especiallypreferred.

In brief, the process comprises the following steps.

Step 1. Producing the solid biologically active material with therequired particle size, suitably by a milling process. The preferredaverage particle size of the solid is 0.01-50 microns, preferably 1-10microns and even more preferably 1-5 microns.

Step 2. Suspending the solid biologically active material in an organicliquid. The liquid is preferably a poor solvent for the solid, that isit will not dissolve large quantities of the solid. The liquid must alsobe immiscible with water, but polar enough to dissolve the prepolymersused in the microencapsulation process.

The liquid preferably contains a dispersant capable of keeping the solidin the liquid but which does not allow the solid to be extracted intothe water when the suspension is dispersed into water. In addition, whenthe suspension is added to water, the dispersant must not allow phaseinversion to occur i.e., the water must not be allowed to be taken intoan emulsion by the organic liquid.

The exact choice of dispersants will depend on the choice of solid andthe liquid but preferred dispersants are non-ionic surfactants which actby steric hindrance and are active only at the solid/organic liquidinterface and do not act as emulsifying agents. Such dispersants aresuitably made up of i) a polymeric chain having a strong affinity forthe liquid and ii) a group which will absorb strongly to the solid.

Examples of such dispersants include phthalocyanine derivatives,polyoxyalklene amine derivatives, polyamine polymers, polyesterpolymers, various derivatives of polycondensed fatty acids, includingmetal derivatives, amine derivatives and ammonium derivatives, allavailable under the tradenames Hypermer and Atlox from ICI AmericasInc., Wilmington, Del., e.g., Atlox LP1, Atlox LP2, Atlox LP3, AtloxLP4, Atlox LP5, Atlox LP6, Atlox PS2, Atlox PS3, Hypermer PS1, HypermerPS2, Hypermer PS3, and Hypermer LP2; and vinylpyrrolidone polymersavailable under the tradename Agrimer AL from GAF such as Agrimer AL-220and Agrimer AL-216.

In general, the range of dispersant concentration used is from about0.01 to about 10% by weight based on the organic phase, but higherconcentration of surfactant may also be used.

Alternatively, the procedures of Steps 1 and 2 may be varied bypreforming a milling process, to reduce the particle size of the solid,after the solid biologically active material is suspended in the organicliquid (media milling).

Step 3: A physical dispersion of a water-immiscible phase in an aqueousphase is prepared. To obtain the appropriate dispersion, the organicphase is added to the aqueous phase, with stirring. A suitabledispersing means is employed to disperse the organic phase in the liquidphase. The means may be any high shear device, so as to obtain a desireddroplet (and corresponding microcapsule particle) size within the rangeof from about 1 to about 200 microns. Preferably the droplet size isfrom about 1 to about 30 microns, most preferably from about 3 to about20 microns, average. Once the proper droplet size is obtained, thedispersion means is discontinued. Only mild agitation is required forthe remainder of the process. The water-immiscible phase comprises thesolid, biologically active compound suspended in the liquid to beencapsulated prepared as described above in Steps 1 and 2. The aqueousphase is comprised of water and a material termed a "protectivecolloid". Preferably it further contains a surfactant.

In general, the surfactant or surfactants in this phase may be anionicor non-ionic surfactants with an HLB range of from about 12 to about 16that is high enough to form a stable oil-in-water emulsion. If more thanone surfactant is used, the individual surfactants may have values lowerthan 12 or higher than 16. However, when combined together the overallhydrophilelipophile balance (HLB) value of the surfactants will be inthe range 12-16. Suitable surfactants include polyethylene glycol ethersof linear alcohols, ethoxylated nonylphenols, naphthalene sulfonates,and the like. Other suitable surfactants include block copolymers ofpropylene oxide and ethylene oxide and anionic/nonionic blends.Preferably the hydrophobic portion of the surfactant has chemicalcharacteristics similar to the organic liquid. Thus, when the organicliquid is an aromatic solvent, the surfactant would suitably be anethoxylated nonphylphenol.

Especially preferred surfactants are Tergitol NP7, Tergitol NP40 andTergitol 15-S-20.

In general, the range of surfactant concentration in the process is fromabout 0.01 to about 10.0 percent by weight, based on the aqueous phase,but higher concentrations of factant may also be used.

The protective colloid present in the aqueous (or continuous) phase mustabsorb strongly onto the surface of the oil droplets. Suitable colloidforming materials include one or more of polyalkylates, methylcellulose, polyvinyl alcohol, polyacrylamide, poly(methylvinylether/maleic anhydride), graft copolymers of polyvinyl alcohol andmethylvinyl ether/maleic acid (hydrolyzed methylvinyl ether/maleicanhydride; see U.S. Pat. No. 4,448,929, which is hereby incorporated byreference herein), and alkali metal or alkaline earth metallignosulfonates. Preferably, however, the protective colloid is selectedfrom alkali metal and alkaline earth metal lignosulfonates, mostpreferably sodium lignosulfonates. Especially preferred colloids alsocontain polyvinyl alcohol.

There must be sufficient colloid present to afford complete coverage ofthe surfaces of all the droplets of the organic liquid. The amount ofprotective colloid employed will depend on various factors, such asmolecular weight, compatibility, etc. The protective colloid can beadded to the aqueous phase prior to the addition of the organic phase,or can be added to the overall system after the addition of the organicphase or the dispersion of it. The protective colloid is generallypresent in the aqueous phase in an amount of from about 0.1 to about10.0 percent by weight.

Any surfactant used in the aqueous phase must not displace theprotective colloid from the surface of the droplets of organic liquid.

If the water-immiscible liquid is a thiocarbamate or a haloacetanilideherbicide, then depending on the intended application or use of thismicroencapsulated product, the compositions of this invention may alsoinclude a herbicide safener or antidote.

Safeners or antidotes, when included, will usually be contained in theorganic or water-immiscible phase.

The preferred average particle size of the droplets of thewater-immiscible liquid containing a biologically active solid in 1-200microns, preferably 1-30 microns and more preferably 3-20 microns.Particle size can be adjusted according to the end use of themicrocapsules by adjusting stirring speed and time, and by the choice ofsurfactants and the amount of surfactants employed.

In order to obtain the microcapsules, the organic liquid and/or thewater must contain one or more materials which can react to form apolymer at the interface between the organic liquid and the water.

In the process described in U.S. Pat. No. 4,285,720, polyisocyanates aredissolved in the organic phase (i.e., at Step 2 in the above procedure)and polymerization takes place by hydrolysis of the prepolymers at thewater/organic liquid interface to form amines which, in turn, react withunhydrolyzed monomers to form the polyurea microcapsule wall. A singlecompound or a mixture of two or more polyisocyanates may be used.Mixtures are preferred. Of the polyisocyanates, polymethylenepolyphenylisocyanate (PAPI), and isomeric mixtures of toluenediisocyanate (TDI) are preferred. Particularly preferred are mixtures ofpolymethylene polyphenylisocyanate with isomeric mixtures of toluenediisocyanate, in a weight ratio of PAPI:TDI of from about 1:30 to about4:1, especially 1:10 to 1:1.

The amount of the organic polyisocyanate used in the process willdetermine the wall content of the microcapsules formed. In general, thepolyisocyanate (or microcapsule wall formed from it) will comprise fromabout 2.0 to about 75.0 percent by weight of the microcapsule. Mostpreferably the wall will comprise from about 4 to about 15% by weight,of the microcapsule.

The dispersion is maintained in a temperature range of from about 20° C.to about 90° C. preferably 40°-60° C. during which the condensationreaction takes place to form the polyurea, at the interfaces between thedroplets of the organic phase and the aqueous phase.

A thiocarbamate or a haloacetanilide herbicide may be used as a solventfor the polyisocyanates. Alternatively, solvents such as xylene may beused (see Canadian Patent 1,094,402).

Another suitable system for forming microcapsules is described in U.S.Pat. No. 4,956,129, in which the polymer is formed from an etherifiedurea-formaldehyde prepolymer in which 50-98% of the methylol groups havebeen etherified with a C₄ -C₁₀ alcohol. Self-condensation of theprepolymer takes place under the action of heat at low pH.

To form the microcapsules, the temperature of the two-phase mixture israised to a value of from about 20° C. to about 90° C., preferably fromabout 40° C. to about 90° C., most preferably from about 40° C. to about60° C. Depending on the system, the pH value may be adjusted to anappropriate level.

The following are examples of preparations of compositions of thisinvention.

GENERAL PROCEDURE

In the first two examples which follow, the compositions were preparedby the following general procedure:

The organic phase was added to the aqueous phase, and an oil-in-wateremulsion was formed by means of a high shear stirrer. The averageparticle size was in the range of 11.0±2 microns. While mild agitationwas maintained, the temperature of the batch was raised to 50° C. over aperiod of 30 minutes, and held at 50° C. for 3 hours. The resultingmicrocapsule suspension was then allowed to cool to room temperature.The additional ingredients were then added and the pH was then adjustedto 11.0 with 50% caustic.

In the third example, the pH of the aqueous phase was adjusted to 2.0.Then the organic phase was added to the aqueous phase, and anoil-in-water emulsion was formed by means of high shear stirrer. Theaverage particle size was in the range of 28±3 microns. While mildagitation was maintained, the temperature of the batch was raised to 50°C. over a period of 30 minutes and held at 50° C. for 3 hours. Theresulting microcapsule suspension was then allowed to cool to roomtemperature. The additional ingredients were then added and the pH wasadjusted to 7.0 with 50% caustic.

EXAMPLE I

14473-27-1

A composition was prepared using the general procedure described abovewith the following ingredients.

    ______________________________________                                        Component            Weight, g.                                                                             Weight %                                        ______________________________________                                        ORGANIC PHASE                                                                 Atrazine (technical grade)                                                                                         16.58                                    Acetochlor (technical grade)                                                                                100.0                                                                                25.51                                    N,N-diallyldichloroacetamide                                                                                        4.33                                    Hypermer LP5                          2.30      9.0                           Hypermer LP1                         1.02       4.0                           Polymethylene polyphenylisocyanate                                                                      2.0        0.51                                     Toluene diisocyanate                 2.299.0                                  AQUEOUS PHASE                                                                 Reax 100M (sodium salt of ligno-                                                                         18.0                                                                                     4.59                                    sulfonic acid, 40% solution in water)                                         Gelvatol 40/10 (PVA, 20% solution                                                                       18.0                                                                                      4.59                                    in water)                                                                     Tergitol NP7 (20% solution in water)                                                                   4.0         1.02                                     Tergitol NP40 (70% solution in water)                                                                 1.0          0.26                                     Water                                35.15            138.8                   ADDITIONAL INGREDIENTS                                                        Attapulgite (attagel 40).sup.1                                                                                      0.98                                    Xanthan gum (Kelzan).sup.1                                                                                         0.07                                     Sodium carbonate.sup.2                                                                                             0.702.7                                  Proxel GXL.sup.3           0.4                                                                                0.10                                          TOTAL                               100.000                                   ______________________________________                                         .sup.1 = suspending agent                                                     .sup.2 = buffering agent                                                      .sup.3 = biocide                                                         

The resulting microencapsulated product had an average particle diameterof 10.0 microns.

EXAMPLE II

14585-26

A composition was prepared using the general procedure described abovewith the following ingredients.

    ______________________________________                                        Component           Weight, g.                                                                             Weight %                                         ______________________________________                                        ORGANIC PHASE                                                                 2-(2-nitro-4-methanesulfonyl-                                                                                  12.50                                        benzoyl)-1,3-cyclohexanedione                                                 Solvesso 200                      28.75        115.0                          Hypermer LP6 (40% solution in                                                                                    8.00                                       hydrocarbons)                                                                 Polymethylene polyphenylisocyanate                                                                      8.0                                                                                    2.00                                       Toluene diisocyanate                                                                                              2.000                                     AQUEOUS PHASE                                                                 Reax 100M (sodium of lignosulfonic                                                                      18.0                                                                                   4.50                                       acid, 40% solution in water)                                                  Gelvatol 40/l0 (PVA, 20% solution                                                                        18.0                                                                                  4.50                                       in water)                                                                     Tergitol NP7 (20% solution in water)                                                                  4.0         1.00                                      Tergitol NP40 (70% solution in water)                                                                1.0          0.25                                      Water                             34.70               138.8                   ADDITIONAL INGREDIENTS                                                        Attapulgite (attagel 40)                                                                                          0.95                                      Xanthan gum (Kelzan)                                                                                              0.07.3                                    Sodium carbonate                    0.68    2.7                               Proxel GXL                    0.10    0.4                                     TOTAL                            100.0000.0                                   ______________________________________                                    

The resulting microencapsulated product had an average particle diameterof 12.5 microns.

EXAMPLE III

14369-21-3

A composition was prepared using the general procedure described abovewith the following ingredients.

    ______________________________________                                        Component           Weight, g.                                                                             Weight %                                         ______________________________________                                        ORGANIC PHASE                                                                 Atrazine (technical grade)                                                                                        10.00                                     Solvesso 200                        23.28      92.7                           Beetle 1050 Resin                    6.68 26.6                                (butylated urea-formaldehyde                                                  prepolymer, 60% solution in butanol)                                          AQUEOUS PHASE                                                                 Petro BAF (sodium dialkylnaphthalen-                                                                  0.8          0.20                                     sulfonate)                                                                    Reax 100M (sodium salt of ligno-                                                                        18.8                                                                                     4.72                                     sulfonic acid, 40% solution in                                                water)                                                                        Water                               53.99            215.0                    ADDITIONAL INGREDIENTS                                                        Attapulgite (attagel 40)                                                                                           0.95                                     Xanthan gum (Kelzan)                                                                                               0.08.3                                   Proxel GXL                    0.104                                           TOTAL                              100.00    398.2                            ______________________________________                                    

The resulting microencapsulated product had an average particle diameterof 28 microns.

In each Example the final product of the process was analyzed bymicroscopy and polarography. The results showed that the suspension ofbiologically active solid was successfully microencapsulated and theaqueous phase was substantially free of the solid.

What is claimed is:
 1. A process for preparing microcapsules containinga solid biologically active compound suspended in liquid which processcomprises:a) preparing a suspension of said compound in an organicliquid which is immiscible with water by either:i) producing a powder ofsaid compound with a particle size of 0.01-50 microns and suspendingsaid powder in said organic liquid, or ii) suspending said compound insaid organic liquid and media milling said compound to a particle sizeof 0.01-50 microns; b) introducing said suspension into water containinga protective colloid and optionally a surfactant capable of maintainingthe organic liquid as droplets in the water without extracting the solidfrom the organic liquid into the water; the organic liquid and/or thewater containing in solution one or more monomers or prepolymers whichcan react to form a polymer at the interface of the organic liquid andwater and in which the organic liquid contains from about 0.01 to about10 percent by weight, based on the total weight of the organic phase, ofa dispersant which functions to keep the solid in the liquid but whichdoes not allow the solid to be extracted into water, is active only atthe solid/organic liquid interface, and does not act as an emulsifyingagent; c) mixing the suspension of organic liquid in the aqueous phaseunder high shear to form an oil-in-water emulsion; and d) adjusting asnecessary the temperature and/or pH of the oil-in-water emulsion suchthat a polymerization reaction takes place to form the microcapsules. 2.A process according to claim 1 wherein the particle size of thebiologically active solid is 1-10 microns.
 3. A process according toclaim 2 wherein the particle size of the droplets of organic liquidafter dispersion in the water is 1-30 microns.
 4. A process according toclaim 1 wherein the biologically active compound is atrazine.
 5. Aprocess according to claim 4 wherein the organic liquid is ahaloacetanilide or thiocarbamate herbicide.
 6. A process according toclaim 5 wherein the organic liquid is acetochlor.
 7. A process accordingto claim 6 wherein the acetochlor contains a safener.
 8. A processaccording to claim 1 in which the protective colloid is an alkalinemetal or alkaline earth metal lignosulfonate.
 9. A process according toclaim 8 wherein the protective colloid is sodium lignosulfonate.
 10. Aprocess according to claim 9 in which the protective colloid containsadditionally polyvinyl alcohol.
 11. A process according to claim 1 inwhich the surfactant in the aqueous phase has an hydrophile-lipophilebalance value of from about 12 to about
 16. 12. A process according toclaim 1 wherein the prepolymer is an organic polyisocyanate dissolved inthe organic liquid which when heated forms a polyurea by hydrolysis ofan isocyanate to an amine which in turn reacts with another isocyanateto form the polyurea.
 13. A process according to claim 12 in which thepolisocyanate is a mixture of polymethylene polyphenylisocyanate and anisomeric mixture of toluene diisocyanate.
 14. A process according toclaim 1 wherein the dispersant is a phthalocyanine derivative, apolyoxyalklene amine derivative, a polyamine polymer, a polyesterpolymer, any of various derivatives of polycondensed fatty acids,including metal derivatives, an amine derivative or an ammoniumderivative.
 15. A process according to claim 1 wherein the prepolymer isa urea-formaldehyde prepolymer in which about 50-98% of the methylolgroups have been etherified with a C₄ -C₁₀ alcohol, and which forms asolid polymer at pH 0-4 at 20-100° C.
 16. A process according to claims15 in which 70-90% of the methylol groups have been etherified withn-butanol.
 17. A process according to claim 15 wherein the solid isatrazine.
 18. A process according to claim 15 wherein the protectivecolloid is sodium lignosulfonate optionally containing polyvinylalcohol.
 19. A process according to claim 1 wherein said microcapsuleshave an average particle size of about 1 to 200 microns.
 20. A processaccording to claim 1 wherein said solid, biologically active compoundhas an average particle size of about 0.01 to 50 microns.
 21. A processaccording to claim 1 in which the dispersant molecule comprises apolymeric chain having a strong affinity for the organic liquid and agroup which will absorb strongly to the biologically active solid.